The present invention relates to a process for preparing 4,6-dichloropyrimidine from 4-chloro-6-hydroxypyrimidine. 4,6-Dichloropyrimidine is a valuable intermediate for preparing crop protection agents.
A number of processes for preparing 4,6-dichloropyrimidine are known, see, for example, WO96/23776, EP-A-697 406, EP-A-745 593, WO 95/29166, DE-A-19 53 129 and GB 2 325 224. However, these processes always start from 4,6-dihydroxypyrimidine.
It is also known (see Res. Discl. n 391, 690-691 (1996)) that 4,6-dichloropyrimidine can be reacted by reacting 4-chloro-6-methoxypyrimidine with a chlorinating agent of the formula R3PCl2.
DE-A44 08 404 describes a process for preparing chloropyrimidines, including inter alia 4,6-dichloropyrimidine. Hydroxypyrimidines are generally mentioned as starting material, but not chlorohydroxypyrimidines. According to this reference, furthermore, chlorination is effected with POCl3 with addition of amines or amine hydrochlorides.
No process for preparing 4,6-dichloropyrimidine starting from 4-chloro-6 hydroxypyrimidine and resulting in the desired product in a simple manner is yet known.
A process for preparing 4,6-dichloropyrimidine which is characterized in that 4-chloro-6-hydroxypyrimidine is reacted with an acid chloride has now been found.
Suitable acid chlorides are organic and inorganic acid chlorides, for example PCl3, POCl3, PCl5, Rxe2x80x94PCl2, Rxe2x80x94PCl4, Rxe2x80x94POCl2 and R3PCl2, where R represents optionally substituted C6-C10-aryl or optionally substituted C1-C10-alkyl, acid chlorides of the formula Rxe2x80x2xe2x80x94COxe2x80x94Cl with Rxe2x80x2=chlorine, C1-C10-alkoxy, C6-C10-aryloxy, xe2x80x94Oxe2x80x94CCl3, xe2x80x94COxe2x80x94Cl, C5-C11-heteroaryloxy with 1 to 3 heteroatoms from the group of N, O and S, where the alkoxy, aryloxy and hetaryloxy radicals may optionally be substituted, and SOCl2.
The acid chlorides are active on their own. In particular, no additions of catalysts are necessary, such as amides (for example diethylformamide), amines or organic phosphorus compounds (see EP-A-95 637).
However, it is possible to add such catalysts which are known in principle.
It is also possible to employ mixtures of acid chlorides, but this is not preferred.
It is furthermore possible to generate the required acid chloride in situ. For example, R3PCl2 can be generated from R3P and chlorine or from R3Pxe2x95x90O and a chlorinating agent, for example PCl3, phosgene or SOCl2.
It is furthermore possible to employ not only isolated 4-chloro-6-hydroxypyrimidine but also a reaction mixture which contains 4-chloro-6-hydroxypyrimidine and originates, for example, from the cleavage of 4-chloro-6-methoxypyridine. The acid chloride to be employed according to the invention can be metered directly into the reaction mixture from the cleavage of 4-chloro-6-methoxypyrimidine.
In general, at least 1 mol of acid chloride per mole of 4-chloro-6-hydroxypyrimidine is employed in the process of the invention. This amount is preferably 1 to 3 mol.
Solvents suitable in principle are those which have no adverse effect on the reaction to be carried out. Examples are aliphatic solvents such as alkanes, cycloalkanes and halogenoalkanes, aromatic solvents such as benzene, xylenes, toluene, chlorobenzenes, benzotrifluoride, p-chlorobenzotrifluoride and anisole, it being possible for the aliphatic and aromatic solvents optionally to be substituted further, nitriles such as acetonitrile and benzonitrile, N-containing solvents such as dimethylformamide, dimethylaceamide, lactams and cyclic ureas, and ethers and polyethers of a wide variety of types. A solvent can be dispensed with if liquid acid chlorides are employed, preferably in excess.
The process of the invention can be carried out, for example, at temperatures in the range 0 to 200xc2x0 C., preferably at 20 to 175xc2x0 C., particularly preferably at 30 to 150xc2x0 C. The pressure is not critical. It can be, for example, 0.1 to 50 bar, preferably 0.5 to 5 bar. Atmospheric pressure is particularly preferred.
The process of the invention can be carried out in various embodiments, for example batchwise, semibatchwise or continuously. One possible procedure is as follows: 4-chloro-6-hydroxypyrimidine is added to an acid chloride with, where appropriate, a solvent. It is then possible to stir at the desired temperature until the conversion to the 4,6-dichloropyrimidine has taken place substantially or completely. It is also possible to meter the acid chloride into 4-chloro-6-hydroxypyrimidine in solution or as suspension. Other procedures are also conceivable.
The working up of the reaction mixture present after the reaction can take place, for example, by extraction of the prepared 4,6-dichloropyrimidine with a solvent and subsequent distillation of the extract. It is also possible to add water to the mixture present after the reaction and then remove 4,6-dichloropyrimidine. It is also possible to distil the complete reaction mixture or firstly carry out a rechlorination with Cl2/PCl3 or PCl5 and then distil. Other embodiments and possible work ups are also conceivable.
The process of the invention for preparing 4,6-dichloropyrimidine is considerably simpler than the prior art processes. It requires no catalysts or auxiliaries such as amides, organic phosphorus compounds, amines or amine hydrochlorides. It can moreover be carried out without solvent if liquid acid chlorides are used, which greatly simplifies the working up.